tbuckley/cabot-search huggingface dataset:
Interaction of race and socioeconomic status as risk modulators of treatment delay and cancer-specific mortality in uterine cancer.
Authors: Larissa H Mattei, Rosa Miller Polan, Julie J. Ruterbusch, Michele L. Cote
Journal: Journal of Clinical Oncology (2022)

5595 Background: The majority of studies of uterine cancer combine high and low-grade histologies and do not sample a diverse cohort of patients. In many studies race is treated as biologic construct, when it may be better thought of as a proxy for socioeconomic inequity and deprivation. Socioeconomic (SE) deprivation may play a significant role in the disease trajectory of women with uterine cancer. Methods: Data were drawn from the Metropolitan Detroit Cancer Surveillance System which covers a tri-county area of approximately 4 million people. We included non-Hispanic Black (NHB) and White (NHW) women diagnosed with uterine cancer between 2010 and 2018. Poorly differentiated and undifferentiated endometrioid, serous, clear cell, mixed, carcinosarcoma and mucinous histologies were considered high grade. Patients diagnosed by death certificate, or with unknown stage or histology were excluded. Socioeconomic status was assessed using the Yost Score, an area-level composite measure of socioeconomic deprivation derived from census-tract data at cancer diagnosis. Lower Yost quintile indicates higher deprivation. Competing risk analysis was used to determine risk of uterine cancer specific mortality (reported as subdistribution hazard ratio [SHR]) and to assess statistical interaction between race and Yost score. Results: A total of 4,840 patients were identified. Race conferred significant increased risk of cancer-specific mortality (SHR 2.11, p &lt; 0.0001). Race and Yost score interacted to increase risk of cancer-specific mortality in NHB women in the lowest Yost quintile (SHR 2.23, p &lt; 0.0001) compared to NHW and NHB women in the highest quintiles. The interaction between race and Yost score persisted only among women with low grade cancers (SHR 1.7, p = 0.04). Time from diagnosis to surgery increased as Yost score decreased. Women in the lowest Yost quintile had lower likelihood of receiving surgery within 6 weeks of diagnosis (OR 0.74, p = 0.001). This effect persisted among women with low grade cancer (NHB OR 0.75, p = 0.014; lowest Yost quintile OR 0.68, p &lt; 0.0001). An association between race, Yost score and delays in time to surgery was not seen among women with high grade cancers. Conclusions: Race and Yost score, an area-based measure of socioeconomic deprivation, are associated with increased cancer-specific mortality risk among women with low grade cancer. NHB race and high socioeconomic deprivation are associated with delayed primary surgery. The interaction between race and socioeconomic deprivation may underlie known disparities in uterine cancer survival, particularly in low grade disease where there is the greatest opportunity for timely curative surgery.
Limited benefit from the addition of immunotherapy to chemotherapy in TKI-refractory EGFR-mutant lung adenocarcinoma.
Authors: Lingzhi Hong, Whitney E Lewis, Susan Varghese, Melvin Rivera, Robyn Du, Pingjun Chen, Haley Kemp, Waree Rinsurongkawong, Sadiq Rehmani, Amy R. Spelman, Yasir Y Elamin, Marcelo Vailati Negrao, Boris Sepesi, Don Lynn Gibbons, J. Jack Lee, Jia Wu, Natalie I Vokes, John Heymach, Jianjun Zhang, Xiuning Le
Journal: Journal of Clinical Oncology (2022)

e21169 Background: The benefit of adding immunotherapy to chemotherapy in EGFR-mutant lung adenocarcinoma (LUAD) with acquired resistance to EGFR tyrosine kinase inhibitors (TKIs) is not fully investigated. This study aimed to explore the outcomes of immunotherapy combinations in such population in a real-world setting. Methods: This retrospective analysis included patients with EGFR-mutant LUAD who progressed on EGFR TKIs and received subsequent therapy with chemotherapy (chemo; n = 84), chemotherapy with immunotherapy (chemoIO; n = 30), chemotherapy plus bevacizumab with or without IO (withBev; n = 42), and IO monotherapy (IO-mono; n = 22). Clinical progression-free survival (cPFS) from the start of the therapy to discontinuation was assessed. Associations of clinical characteristics with cPFS were evaluated using univariable and adjusted Cox regression models. Results: A total of 178 patients (mean age = 62.6; 57.9% females) with a median cPFS (mcPFS) of 4.9 (95% CI: 4.4-5.4) months with 162 (91%) progression events. There was no difference in cPFS between chemoIO vs chemo groups (5.3 months vs 4.8, P = 0.8). Compared to the chemo group, patients who were treated withBev trended towards better PFS (6.1 months vs 4.8; P = 0.3; HR 0.79; 95% CI: 0.52-1.20;), while patients with IO-mono had inferior PFS (2.2 months; P = 0.001; HR 2.22; 95% CI: 1.37-3.59). Patients who were administered one-line of TKI prior to subsequent therapy acquired better PFS when compared to those with multiple prior TKIs (5.2 months vs 4.5; P = 0.011; HR 0.66; 95% CI: 0.48-0.91). The significance remained the same after adjusted by other clinicopathological variables including post-TKI treatment strategies and metastatic status (P = 0.005). Furthermore, among the chemoIO group, patients with PD-L1 expression had better PFS (n = 15, 7.7 months vs 4.5, P = 0.04; HR 0.36; 95% CI: 0.13-0.96) than those without PD-L1 expression (n = 6). However, PD-L1 was not associated with PFS among the patients treated with chemoIO plus bevacizumab. Brain or liver metastases were associated with worse PFS. Conclusions: Immunotherapy adds limited benefit when combined with chemotherapy in TKI-refractory EGFR-mutant LUAD. Chemotherapy +/- bevacizumab are reasonable treatment options for these patients.
DIPG-49. International preclinical drug discovery and biomarker program informing an adoptive combinatorial trial for DMG
Authors: Javad Nazarian, Matthew Dun, Lindsay Kilburn, Sebastian Waszak, Nicholas Vitanza, Andrea Franson, Mike Prados, Eric Raabe, Ron Firestein, Alexander Beck, Amanda Saratsis, Barak Rotblat, Dannis van Vuurder, Jessica Foster, Esther Hulleman, Cassie Kline, Nalin Gupta, Jason Cain, Carl Koschmann, Sabine Muller
Journal: Neuro-Oncology (2022)

Abstract INTRODUCTION: DMG-ACT (DMG- multi-arm Adaptive and Combinatorial Trial) will implement an innovative clinical trial design of combinatorial arms for patients with DMG at all disease stages, that is adaptive to pre-clinical and correlate data generated in eight collaborating institutions. The goal of the team is to rapidly identify and validate i) promising drugs and drug combinations for clinical use, and ii) predictive biomarkers of promising drugs. METHODS: In vitro (n=30) and in vivo (n=8) models of DMG across fourteen institutions were used to assess single and combination treatment of over 80 drugs and drug combinations. Predictive biomarkers of response for top candidate drugs were identified using extensive molecular assays including proteomics, CRISPR, RNAseq, ELISA, FACS, and IHC. RESULTS: Inhibitory concentration (IC50) of all drugs were established and validated across all participating sites. In vivo validation of single and combination drug assays confirmed drug efficacy as increased survival for: ONC201 (p=0.01), ONC206 (p=0.01), ONC201+ONC206 (p=0.02), ONC201+panobinostat (p=0.01). Marizomib was highly toxic in murine PDX and zebrafish larvae assays. Murine pharmacokinetic analysis showed peak brain levels of ONC201, and ONC206 above pre-clinical IC50 concentrations. Molecular testing and analyses of existing drug screen across 578 cancer cells validated mitochondrial stress and additional proteins, as the main targets induces by ONC201/6. CONCLUSION: Thorough preclinical testing in a multi-site laboratory setting identified promising therapeutics for DMGs, resulting in launch of two clinical trials (PNOC022, ONOC023). Validation of identified biomarkers are ongoing using clinical specimen as well as in vivo PDX models.
QOL-09. SyMon-SAYS: A symptom monitoring and reporting program for children with cancer
Authors: Jin-Shei Lai, Sally Jensen, Megan Urban, Stewart Goldman, Alicia Lenzen
Journal: Neuro-Oncology (2022)

Abstract Unrelieved symptom burden due to cancer treatments can lead to poor psychosocial functioning and decreased health-related quality of life (HRQOL) for patients and their families. Barriers at the patient, healthcare provider and system levels can contribute to poor symptom management. Funded by the US National Cancer Institute, we have developed the Symptom Monitoring &amp; Systematic Assessment and Reporting System in Young Survivors (SyMon-SAYS) program. SyMon-SAYS is a technology-based program with the potential to minimize symptom management barriers by routinely collecting and interpreting patient-reported outcomes in pediatric oncology ambulatory settings in a manner that is efficient, actionable by clinicians, supports engagement of patients and families with their health and care, and improves clinical processes and outcomes. This is a single institution modified waitlist control 16-week randomized trial of 200 children (ages 8-17) with cancer and their parents/guardians. Participants in the intervention phase will complete a symptom checklist weekly via the electronic health record patient portal. Scores exceeding a pre-defined threshold will trigger an alert to the treatment team, which will review the report and take appropriate actions. Participants will complete a separate battery of questionnaires assessing HRQOL at baseline and weeks 8 and 16. The recruitment is in progress. As of today, we have recruited 57 patients/parents. 29 completed 16-week study (15 intervention &amp; 14 wait-list). Preliminary results showed SyMon-SAYS system was easy (92%) and convenient (85%) to use. Parents were satisfied (74.1%) with the SyMon-SAYS program. Comparing to the waitlist control, intervention group parents reported significantly less concerns on not having enough time to discuss their child’s symptoms with treating clinicians (p=0.0022), and disagreed that it is not necessary to treat their child’s symptoms as they will go away (p=0.04). We anticipate completing the recruitment by the end of 2023.
Cardiomyocyte fusion as a new mechanism contributing to pathological cardiac hypertrophy
Authors: A Colliva, S Vodret, W Bongiovanni, S Zacchigna
Journal: Cardiovascular Research (2022)

Abstract Funding Acknowledgements Type of funding sources: None. Introduction Pathological cardiac hypertrophy is a maladaptive remodeling response, induced by multiple pathogenetic mechanisms, including genetic mutations and hypertension. Despite the high prevalence of this condition, the precise mechanisms driving its onset and progression remain elusive. Recent evidence indicates that homotypic cell fusion between cardiomyocytes occurs in the heart of lower vertebrates in response to injury, as well as in the rodent heart during the first week after birth, when cardiomyocyte size and ploidy increase. We hypothesized that homotypic fusion of cardiomyocytes could be triggered by pressure overload and contribute to cardiac hypertrophy. Methods and Results We exploited a genetic mouse model (MHC-CreER/mTmG mice) to genetically label individual cardiomyocytes by either red or green fluorescence. These mice express a tamoxifen inducible Cre recombinase (CreER) under the control of the myosin heavy chain 6 promoter (MHC). Controlled injection of tamoxifen resulted in a mosaic heart, composed by either red or green cardiomyocytes. In this genetic background, we performed transverse aortic constriction (TAC) to induce cardiac hypertrophy and analyzed cardiomyocyte size and fluorescence at one month. The systematic analysis of more than 5000 cardiomyocytes from 6 independent experiments showed a significant increase in the number of yellow cardiomyocytes after TAC compared to sham hearts, consistent with cell-cell fusion events occurred between green and red cardiomyocytes. Moreover, these yellow hypertrophic cardiomyocytes displayed a higher rate of polynucleation, with many cells bearing three or more nuclei. Conclusions and future perspective Collectively, these data point to cardiomyocyte fusion as a new mechanism responsible for to the onset of cardiac hypertrophy upon pressure overload. We cannot exclude that yellow, polynucleated cardiomyocytes derived from the heterotypic fusion between a green cardiomyocyte and other red cell types. To rule out this possibility we are currently performing a new a set of experiments in which 100% of cardiomyocytes are labelled in green. In the case of homotypic fusion, we should not observe any yellow cells upon TAC. Proving that cardiomyocyte fusion contributes to cardiac hypertrophy in response to increased pressure load and dissecting the underlying molecular mechanisms will pave the way to novel strategies to both prevent and revert this highly prevalent pathological condition.
Silent myocardial infarction in non-insulin dependent type 2 diabetes mellitus patients with low adherence to blood glucose monitoring
Authors: K Viligorska
Journal: Cardiovascular Research (2022)

Abstract Funding Acknowledgements Type of funding sources: None. Background Decompensated diabetic patients frequently suffer from ischemic complications including silent ST-elevation myocardial infarction (STEMI). Purpose Aim of this study was to define prognostic value of low adherence to self-monitoring of blood glucose (SMBG) in type 2 diabetes mellitus (T2DM) patients as risk factor that leads to silent STEMI. Methods The electronic search in Cochrane Library, Scopus, PubMed and Web of Science for the period of 2016-2018 systematic literature review concentrated on types of educational interventions administered before SMBG in type 2 diabetes mellitus patients who are not using insulin was conducted. 18 studies were eligible for inclusion. We included all randomized controlled trials on SMBG education in T2DM patients compared with standard care in adult patients. As a proof of self-efficacy after SMBG glycated hemoglobin (HbA1c) was chosen as primary endpoint. Study group: 12 (7 females, 5 male, age 56-85 years) T2DM patients with non-insulin dependent diabetes for &amp;gt;5 years, low skills of SMBG that were admitted to surgery department with diabetic foot ulcers for the period of August 2019-September 2019 developed silent STEMI. Control group 10 (5 females, 5 males) T2DM patients that corresponded by age and study parameters, but did SMBG once a week via individual glucometers. Blood glucose, troponin I (cTnI) levels were registered. Statistical analysis:IBM SPSS Statistics v.23, RevMan5. Results During systematic review evidence indicated that a SMBG education was associated with more stress and lower rate in well-being and treatment satisfaction in comparison to a standard care (random-effects SMD: 0.45; 95% CI: 0.25-0.65; P &amp;lt; 0.0001). Depending on type of SMBG record subgroup analysis indicated that SMBG skills depend on SMBG education delivery. Patients that did feet checking, SMBG at least once a week had lower risk of complications development (P&amp;lt;0.05). STEMI development was associated with low SMBG in a form of checking only at visits to general practitioner (HR 1.15, 95% CI:1.04-1.13). Mean level of cTnI for study group patients was 0.045 ng/ml with no specific cardiac complaints. Conclusions There is a higher risk of silent ST-elevation myocardial infarction development in diabetic patients that have low SMBG skills) due to lacking information about importance of self-monitoring of blood glucose level as a predictor of cardiovascular complications.
Minority Representation in studies cited as references in National Comprehensive Cancer Network (NCCN) Guidelines for Prostate Cancer.
Authors: Zhong Zheng, Lang Qu, Heyue Du, Chao Y. Wang, Xi Cao, Yujun Xiong, Barbara Yim, Shweta Gupta
Journal: Journal of Clinical Oncology (2022)

e18511 Background: Prostate cancer (PC) has a higher incidence, higher lifetime risk, higher risk of progression and lower overall 5-year survival in African American (AA) men compared to Caucasian men. Historically AA men have been under-represented in clinical studies that may prevent some AA men with PC to receive appropriate therapies. We aim to estimate the AA representation in studies cited in national guidelines for PC. Methods: We retrospectively reviewed all listed references in the National Comprehensive Cancer network (NCCN) Prostate cancer guidelines version 2.2021. All cited papers were reviewed for patient level data on racial or ethnic distribution in the study population. Subgroup analysis was performed by subheadings in the guidelines for Black/African American (AA) representation in each topic of discussion. Duplicate studies in the same section were excluded. Results: A total 836 references were screened of which 167 (20%) reported patient race/ethnicity distribution. Overall, 2,711,194 patients were included in reported studies of which 2,263,936 (83.5%) were Caucasian, 12.6% AA and 3.9% others. A total 26 studies reported 20% or more AA of which 14 were under 500 patients only. While 72 studies included over 1000 patients, only 9 of them had over 20% AA patients. Only 1 study (72 patients) out of 12 for systemic therapy in castration-naïve PC reported ethnicities. For Castration resistant PC, ethnicity data was available for 152 patients (3 of 10 studies), 771 patients (2 of 11 studies) and 1200 patients (1 of 4 studies) in abiraterone, enzalutamide and apalutamide studies respectively with 47.4%, 9.2% and 5.7% AA respectively. Olaparib, rucaparib, pembrolizumab and bisphosphonates studies reported 1.4%, 6.3%, 7% and 5.7% AA respectively. Further subgroup analysis is presented in Table. Conclusions: Race/ethnicity data is not reported widely in clinical studies. The overall AA representation remains very low which is also an underestimation since about 80% studies did not report patient ethnicities. Clinical investigators should be encouraged to report racial representation in studies which will help personalize cancer care for African Americans who are at high risk.[Table: see text]
Sequential analysis of macro molecules accessibility unveils altered chromatin solubility patterns and epigenomic dysfunction in prostate cancer
Authors: G. Albo, F. Ripa, L. Rocchini, V. Rosti, C. Petrini, G. Lembo, R. Quadri, J. Hariprakashf, F. Lucini, M. Maggioni
Journal: European Urology (2022)
Impact of diet on ten-year absolute cardiovascular risk in a prospective cohort of 94 321 individuals: A tool for implementation of healthy diets
Authors: Emilie W. Kjeldsen, Jesper Q. Thomassen, Katrine L. Rasmussen, Børge G. Nordestgaard, Anne Tybjærg-Hansen, Ruth Frikke-Schmidt
Journal: The Lancet Regional Health - Europe (2022)

An unhealthy diet is a major risk factor for cardiovascular disease attributing to the burden of non-communicable diseases. Current dietary guidelines are not sufficiently implemented and effective strategies to encourage people to change and maintain healthy diets are lacking. We aimed to evaluate the impact of incorporating dietary assessment into ten-year absolute risk charts for atherosclerotic cardiovascular disease (ASCVD).In the prospective Copenhagen General Population Study including 94 321 individuals, we generated sex-specific ten-year absolute risk scores for ASCVD according to adherence to dietary guidelines, using a short and valid food frequency questionnaire. To account for competing risk, we used the method of Fine-Gray.Non-adherence to dietary guidelines was associated with an atherogenic lipid and inflammatory profile. Ten-year absolute risk of ASCVD increased with increasing age, increasing systolic blood pressure, and decreasing adherence to dietary guidelines for both sexes. The highest ten-year absolute risk of ASCVD of 38% was observed in men aged 65-69 years who smoked, had very low adherence to dietary guidelines, and a systolic blood pressure between 160 and 179 mmHg. The corresponding value for women was 26%. Risk charts replacing dietary assessment with non-HDL cholesterol yielded similar estimates.Incorporation of a short dietary assessment into ten-year absolute risk charts has the potential to motivate patients to adhere to dietary guideline recommendations. Improved implementation of national dietary guidelines must be a cornerstone for future prevention of cardiovascular disease in both younger and older individuals.The Lundbeck Foundation (R278-2018-804) and the Danish Heart Foundation.
Clinical characteristics and outcomes of newly diagnosed patients with human immunodeficiency virus-associated lymphoma administered highly active antiretroviral therapy: Central and Western China AIDS Lymphoma League 001 study (cw-CALL 001).
Authors: Chaoyu Wang, Jun Liu, Haike Lei, Yongzhong Wu, Yao Liu
Journal: Journal of Clinical Oncology (2022)

e19535 Background: HIV-associated lymphoma is the most common subtype of HIV-associated cancers, with a very low incidence. To date, there are only few retrospective studies analyzing the clinical features and prognosis of HIV-associated lymphoma. Therefore, we performed a study to analyze the clinical characteristics and outcomes of newly diagnosed HIV-associated lymphoma patients in our center, as the largest HIV-associated lymphoma cohort in China so far. Methods: Totally 107 newly diagnosed HIV-associated lymphoma patients in Chongqing University Cancer Hospital, Southwest China, from July 2008 to August 2021, were analyzed. Results: In the 107 HIV-associated lymphoma cases, median age was 49 years (range: 23–87 years), and more patients were male (87.9%). Most patients had elevated lactate dehydrogenase (LDH) (78.5%), elevated β 2 -MG (91.6%), advanced Ann Arbor stage (73.8%) and high IPI score (IPI score: 3-5) (62.7%) at diagnosis. Totally 46 patients (43%) had one or more sites of extranodal involvement, of whom 24 (22.4%) possessed two or more extranodal sites. Median CD4 + T cell count at diagnosis was 191/μl (range: 4-1022); 84 patients (78.5%) were on combination antiretroviral therapy (cART) at lymphoma diagnosis. Of the 72 patients evaluated at the end of treatment, the overall response rate (ORR) was 81.9% (59/72); 29 (40.3%) cases achieved complete response (CR), 30 (41.7%) had partial response (PR) and 9 (12.5%) experienced progressive disease (PD). In 99 HIV-associated lymphoma cases with complete follow-up data (median follow-up of 44.5 months [range: 2-160 months]), median PFS and OS were 36.0 months and not reached, respectively. The overall 5-year PFS and OS rates were 46.9% and 53.4%, respectively. Compared with individuals not administered anti-lymphoma treatment or administered less than 3 cycles anti-lymphoma therapy, those who received standardized anti-lymphoma therapy (≥3 cycles) showed improved PFS ( p=0.0006) and OS ( p&lt;0.0001). In patients administered systemic anti-lymphoma therapy, the overall 2-year PFS rates for chemotherapy and R-chemotherapy were 29.5% and 67.1%, respectively (HR=0.44, 95%CI 0.210-0.927; p=0.020). The overall 2-year OS rates for chemotherapy and R-chemotherapy were 51.9% and 73.1%, respectively (HR=0.42, 95%CI 0.183-0.969; p=0.042). Conclusions: Overall, these data indicated that HIV-associated lymphoma has aggressive characteristics, including advanced Ann Arbor stage, high IPI score, more extranodal involvement and elevated LDH. Survival is significantly improved due to the wide use of cART and chemoimmunotherapy. Standardized anti-lymphoma therapy is significantly associated with superior outcomes. Clinical trial information: ChiCTR2100054581.